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Role of NO-cGMP-PKG signalling in the protection of cardiac myocytes subjected to hypoxia/reoxygenation [Abstract]

Gorbe, A., Giricz, Z., Szunyog, A., Baxter, Gary Francis, Csont, T. and Ferdinandy, P. 2008. Role of NO-cGMP-PKG signalling in the protection of cardiac myocytes subjected to hypoxia/reoxygenation [Abstract]. Journal of Molecular and Cellular Cardiology 44 (4) , p. 808. 10.1016/j.yjmcc.2008.02.232

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Abstract

Nitric oxide (NO) is a cytoprotective molecule and may act via the cGMP-protein kinase G signalling pathway activating the soluble-guanylate-cyclase (GC). The B-type natriuretic peptide (BNP) activates the particular GC and probably acts via the same pathway. The aim of the present study was the exploration of the downstream signalling pathway of cGMP signalling. Therefore, primary cardiomyocyte cultures prepared from newborn rats were subjected to 3 h hypoxia and 2 h reoxygenation protocols. The following treatments were applied during the protocol: (1) untreated control, (2) cGMP analogue 8Br-cGMP, (3) 8Br-cGMP and the protein-kinase-G inhibitor KT5823 (KT), (4) KT, (5) NO donor S-nitrozo-penicillamine (SNAP), (6) SNAP and KT, (7) BNP, and (8) BNP + KT. Viability tests were done in all groups with trypane blue staining. After simulated ischemia and reoxygenation, cell death found to be 34%, which was inhibited by 8Br-cGMP (13%, p < 0.001), SNAP (18%, p < 0.05), or BNP (12%, p < 0.001), respectively. The protection was inhibited by KT in each case. PKG activity of cardiomyocytes was tested using detection of phosphorylation of PLB by Western blot. The following groups were tested after hypoxia: (1) untreated control (2) protein kinase A inhibitor KT5720 (KTA), (3) BNP + KTA, (4) BNP + KTA + KT (5) 8Br-cGMP + KTA, and (6) 8Br-cGMP + KTA + KT. Ratio of pPLB/PLB significantly increased after administration of both BNP and 8Br-cGMP, which was abolished by KT. We conclude that increasing cGMP by activation of soluble or particulate gulanylate cyclase exerts cytoprotective effect via a common downstream pathway of PKG signalling in cardiac myocytes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Uncontrolled Keywords: NO-cGMP-PKG; Hypoxia/reoxygenation; Cardiac myocyte
Publisher: Elsevier
ISSN: 0022-2828
Last Modified: 04 Jun 2017 01:57
URI: http://orca-mwe.cf.ac.uk/id/eprint/6531

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